Editors' note: Idiopathic intracranial hypertension: The veno glymphatic connections

In the article “Idiopathic intracranial hypertension: The veno glymphatic connections,” Lenck et al. hypothesized that idiopathic intracranial hypertension (IIH) may be triggered by an initial impairment in interstitial fluid (ISF) transport from the glymphatic system to the dural venous sinuses, speculating that a specific subtype of aquaporin is involved in this transport. In response, Drs. De Simone and Ranieri argue that the proposed asymptomatic primary impairment of ISF/CSF outflow via “aquaporin-4” dysfunction is unlikely. They cite literature questioning the existence of the glymphatic system as an ISF/CSF outflow route; they also note that intraventricular tracer drainage occurs through nasal lymphatics and not venous sinuses in rat models, that vascular arachnoid granulations (AGs) can be seen without IIH, that sinus walls should withstand CSF pressures higher than those associated with asymptomatic outflow dysfunction, and that intracranial pressure (ICP) returns to fully physiologic values in patients with IIH responding to sinus stenting. In their reply, the authors clarify that their hypothesis relates to some unknown aquaporin, not aquaporin-4, and note that although direct discharge of glymphatic fluid into venous blood has not been documented, venous CSF outflow has also been questioned by other studies. They caution against extrapolating CSF physiology findings from animals to humans. Although conceding that AGs may be incidentally found, they explain that their term “vascular” AGs refers to a specific type of AG mostly seen in the transverse sinus, which may permit a connection between perivascular spaces of large cortical veins and dural venous sinuses, thereby mediating glymphatic-to-venous ISF/CSF flow. Furthermore, they present arguments in favor of sinus stenoses in IIH being due to compression by congested brain and CSF, with stent placement reestablishing direct reabsorption of CSF into the sinuses, thereby normalizing ICP and relieving symptoms. Drs. Kronenberg and Kunte write in support of the hypothesis. With respect to the authors' speculation that chronic CSF overflow in the olfactory bulb sheaths may cause CSF rhinorrhea by eroding the cribriform plate, they note that olfactory dysfunction is an underrecognized presentation of IIH and that dysfunction of the extensive lymphatic network around the olfactory nerves was postulated to be causally linked to IIH in a previous article. In response, the authors present arguments in favor of most patients with idiopathic CSF leaks having underlying IIH, suggesting that the leaks—such as CSF rhinorrhea—represent overflow from the overburdened lymphatic CSF outflow pathway, with the consequent CSF diversion relieving IIH symptoms. They argue that surgical repair of such leaks can potentially reactivate this cycle unless the patient is concurrently treated for underlying IIH.